On August 12, 2019 Saul Priceman, Ph.D., City of Hope assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation, and his research team have received a $9.28 million award from the California Institute for Regenerative Medicine (CIRM) to support a chimeric antigen receptor (CAR) T cell phase 1 clinical trial for the treatment of women with HER2-positive breast cancer that has spread to the brain (Press release, City of Hope, AUG 12, 2019, View Source [SID1234538603]).

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HER2 refers to a protein – human epidermal growth factor receptor-2 – which is found on the cell surface of breast cancer cells and drives cancer progression. About 20% of breast cancer patients are HER2-positive, according to the American Cancer Society.

The trial, which opened for enrollment in the fall of 2018 and whose lead clinical investigator is Jana Portnow, M.D., City of Hope associate clinical professor in the Department of Medical Oncology & Therapeutics Research, is testing the safety and effectiveness of the CAR T cell therapy for breast cancer patients with brain metastases who are not effectively being controlled with other therapies. It is estimated that nearly half of all women with HER2-positive breast cancer will eventually develop brain metastases.

"Our team’s goal is to develop a novel therapy for breast cancer patients with brain metastases who currently have no other effective treatments," Priceman said. "This is a beautiful example of how early support from private donors and foundations helped to develop a therapy and initiate a trial we were desperate to bring to patients, and now this CIRM award funds the entire clinical trial and helps to leverage the knowledge gained here to further advance this therapy."

CAR T cells are a cell-based type of immunotherapy in which a patient’s own T cells are reprogrammed to actively seek out and destroy cancerous cells. For this trial, the patient’s T cells will be isolated from the blood and genetically engineered to express a CAR that allows these immune cells to target and eradicate HER2-positive cancer cells. Patients receive CAR T cells directly to the ventricles of their brains, which is an administration route that was first attempted successfully at City of Hope. City of Hope patents covering the HER2 CAR were licensed to Mustang Bio in 2017.

City of Hope, a recognized leader in CAR T cell therapies, has treated more than 350 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world – it currently has 20 ongoing CAR T cell clinical trials, and has just initiated trials for patients with solid tumors, including prostate cancer.

The trial’s key investigators include City of Hope’s Stephen J. Forman, M.D., director, T Cell Therapeutics Research Laboratory and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation; Christine Brown, Ph.D., deputy director, T Cell Therapeutics Research Laboratory and the Heritage Provider Network Professor in Immunotherapy; and Behnam Badie, M.D., chief of City of Hope’s Division of Neurosurgery and Heritage Provider Network Professor in Gene Therapy. The award also includes City of Hope’s Russel Rockne, Ph.D., Vanessa Jonsson, Ph.D., Ammar Chaudhry, M.D., as well as collaborations with University of Southern California’s Peter Kuhn, Ph.D., and California Institute of Technology’s Lior Pachter, Ph.D.

CIRM funded early preclinical work related to this study, which was important in optimizing the therapy for the eventual Food and Drug Administration approval for permission to start a clinical trial. City of Hope also highlights Eli Khouri, Steve Meringoff, Zach Horowitz, Jody and Gary Marsh, The Kenneth T. and Eileen L. Norris Foundation and Gateway for Cancer Research for their support of this program.

On August 12, 2019 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics, targeting infectious diseases and cancers based on its proprietary arenavirus platform, reported recent clinical progress highlights and financial results for the second quarter ended June 30, 2019 (Press release, Hookipa Biotech, AUG 12, 2019, View Source [SID1234538622]).

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"In the second quarter of 2019, HOOKIPA achieved a number of major milestones, including clearance to initiate our first clinical trial in immuno-oncology and acceptance by Gilead of a set of 10 HBV viral vectors for further testing," stated Joern Aldag, HOOKIPA’s Chief Executive Officer. "With the FDA’s clearance of our IND application for HB-201, we are advancing our oncology program into clinical development, and are also aiming to demonstrate that our technology can effectively super-charge the natural defense mechanisms in humans and deliver prevention or cure for the benefit of seriously ill patients."

R&D Pipeline Update and Clinical Progress

HB-101, a prophylactic vaccine for cytomegalovirus
HOOKIPA’s lead product candidate in infectious diseases, HB-101, is in a Phase 2 clinical trial in cytomegalovirus-negative patients awaiting kidney transplantation from living cytomegalovirus-positive donors. The majority of sites have been activated and HOOKIPA expects safety and immunogenicity data from the first cohorts enrolled in the first half of 2020, with preliminary efficacy data to follow in the second half of 2020.

HB-201 and HB-202, a program for the treatment of HPV associated cancers
In July 2019, HOOKIPA announced that its Investigational New Drug (IND) Application for a Phase 1/2 clinical trial of HB-201, a TheraT-based immunotherapy for the treatment of Human Papilloma Virus (HPV)-positive cancers, became effective following the clearance by the U.S. Food and Drug Administration (FDA). HOOKIPA plans to initiate a Phase 1/2 clinical trial of HB-201 in patients with treatment-refractory HPV16+ cancers in the second half of 2019. This will be HOOKIPA’s first clinical trial in immuno-oncology.

In addition, HOOKIPA intends to file an IND application with the FDA for HB-202 in the first half of 2020, and to commence a Phase 1/2 trial combining HB-201 and HB-202, both with and without a checkpoint inhibitor, in patients with treatment-refractory HPV16+ cancers in late 2020.

Strategic collaborations

Progress under Gilead collaboration for therapeutic hepatitis B virus (HBV) and human immunodeficiency virus (HIV)
In May 2019, HOOKIPA achieved a $2m research milestone for HBV by designing and delivering 10 research-grade vectors to Gilead Sciences, Inc., or Gilead, along with the characterization of these vectors and delivery of a data package for the HBV program. These research vectors will be subject to further pre-clinical testing in order to validate a clinical candidate for novel combination therapies for the treatment of HBV. This follows the delivery of 14 research-grade vectors for the HIV program in January 2019.

Board and management

David Kaufman joined HOOKIPA’s Board of Directors
In April 2019, HOOKIPA announced the appointment of David R. Kaufman, M.D., Ph.D., to its Board of Directors. Dr. Kaufman currently serves as Chief Medical Officer of The Bill & Melinda Gates Medical Research Institute. Dr. Kaufman’s expertise as an immunologist and in oncology research and development are expected to be a tremendous addition to help maximize the potential of HOOKIPA’s proprietary arenavirus platform to target infectious diseases and cancers.

Second Quarter 2019 Financial Results

HOOKIPA’s net loss for the three months ended June 30, 2019 was $12.1 million, compared to a net loss of $5.8 million for the three months ended June 30, 2018.

Revenue was $4.1 million for the three months ended June 30, 2019, compared to $0.6 million for the three months ended June 30, 2018. The increase was due to recognition of revenue under the Collaboration Agreement with Gilead.

HOOKIPA’s research and development expenses for the three months ended June 30, 2019, were $13.9 million, compared to $6.2 million for the three months ended June 30, 2018. The primary driver of the increase was an increase in direct research and development expenses of $6.4 million. Direct research and development expenses increased primarily due to the preparation costs of clinical trials for HOOKIPA’s HB-201 and HB-202 programs and the expansion of earlier stage programs. In addition, costs related to HOOKIPA’s collaboration with Gilead contributed to the increase in direct expenses. Internal research and development expenses increased by $1.3 million, primarily as a result of increased research and development headcount.

General and administrative expenses for the three months ended June 30, 2019 were $3.8 million, compared to $1.4 million for the three months ended June 30, 2018. The increase was mainly due to the growth in headcount in HOOKIPA’s general and administrative functions and an increase in professional and consulting fees as well as costs associated with ongoing business activities and costs to operate as a public company.

HOOKIPA’s cash and cash equivalents as of June 30, 2019 were $135.2 million compared to $48.6 million as of December 31, 2018. The increase was primarily attributable to $37.3 million in net proceeds received from the issuance of shares of Series D convertible preferred stock in February 2019, and $74.6 million in net proceeds received from

HOOKIPA’s initial public offering in April 2019, offset by cash used in operating and investing activities. On April 23, 2019, HOOKIPA completed an initial public offering of its common stock by issuing 6.0 million shares of its common stock, at $14.00 per share.

Upcoming Investor Events

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· Bank of America Merrill Lynch Global Healthcare Conference, September 18-20, 2019

On August 12, 2019 Harvard University and Merck are reported a collaboration that will provide significant research funding for up to four years to support immuno-oncology research led by Arlene Sharpe, MD, PhD, at Harvard Medical School (HMS) (Press release, Merck & Co, AUG 12, 2019, View Source [SID1234538604]). Sharpe, the George Fabyan Professor of Comparative Pathology and chair of the HMS Department of Immunology, will collaborate with researchers at Merck on a major project aiming to discover novel aspects of the immune system that may be targeted in future treatments for cancer.

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"This collaborative project aims to discover and validate novel regulators of immune responses," said Dr. Sharpe. "Immunotherapies such as checkpoint inhibitors have revolutionized the treatment of cancer, but my lab is deeply interested in understanding why some patients do not respond or develop resistance to those interventions. My hope is that by defining mechanisms that inhibit immune responses to tumors, we will identify very important druggable targets and new approaches to improve cancer immunotherapy."

The funding will support the work of scientists in the lab of Dr. Sharpe, who is a renowned leader in the field of tumor immunology. She is a member of the National Academy of Sciences and the National Academy of Medicine, and the recipient of numerous awards including the Warren Alpert Foundation Prize in 2017 for her contributions to the discovery of the PD-1 pathway.

"Crucial insights into patient responses and outcomes may be gained through the study of fundamental biological mechanisms," said Isaac Kohlberg, Harvard’s Chief Technology Development Officer and Senior Associate Provost. "The complexity and promise of immuno-oncology presents a prime opportunity for Harvard’s top scientists to advance discovery through an academic-industry collaboration. Through this project, the Sharpe Lab is setting its sight on innovations that may contribute to dramatic improvements in patient care."

Under the agreement spearheaded by Harvard’s Office of Technology Development, Merck will have the option to negotiate an exclusive license to innovations arising from the research collaboration to develop these discoveries toward potential treatments for patients.

"Collaboration with leading scientific groups is an integral part of Merck’s discovery strategy," said Dr. Nick Haining, vice president for oncology discovery at Merck Research Laboratories. "We look forward to working with Dr. Sharpe’s team to investigate new ways to harness the immune system for therapeutic advances."

On August 12, 2019 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on developing curative cell therapies for cancer, reported financial results and corporate updates for the second quarter ended June 30, 2019, and provided recent activities (Press release, Unum Therapeutics, AUG 12, 2019, View Source [SID1234538624]).

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"During the quarter, we advanced our preclinical and clinical pipeline programs that are designed to improve the targeting and functionality of T cells to expand their use in hematologic and solid tumor cancers," said Chuck Wilson, President and Chief Executive Officer of Unum. "Today, we reported preliminary results from Cohort 3 of the Phase 1 trial with ACTR707 in patients with relapsed or refractory non-Hodgkin lymphoma. We are very encouraged by the results from this trial that support our progress towards developing a competitive program with complete responses achieved in five of the 14 patients treated and no reported adverse events of cytokine release syndrome or severe neurotoxicity. Patient enrollment in Cohort 4 is now complete and we anticipate providing results from this cohort later this year. Our ACTR and BOXR platform initiatives in solid tumors also continued during the quarter, with Phase 1 trial enrollment activities progressing on our ACTR707 program in patients with HER2+ solid tumors. Our BOXR platform is designed to improve the functionality of engineered T cells by incorporating a "bolt-on" transgene to overcome resistance of the solid tumor microenvironment to T cell attack, and we are pleased to advance our first candidate from this platform, BOXR1030, towards clinical trials."

Recent Program and Corporate Highlights

ACTR707 Hematologic Program Highlights:

Preliminary results from Cohort 3 from the Phase 1 trial (ATTCK-20-03) in non-Hodgkin lymphoma: Today, Unum provided preliminary results from patients treated in Cohort 3 in ATTCK-20-03, a Phase 1, multicenter, open-label, single-arm, dose-escalating trial evaluating ACTR707 in combination with rituximab in patients with relapsed/refractory CD20+ B cell non-Hodgkin lymphoma (r/r NHL) who, among other criteria, received adequate prior anti-lymphoma therapy, including anti-CD20 monoclonal antibody and chemotherapy. Among the 14 patients treated in Cohorts 1, 2 and 3, the majority (93%) were diagnosed with diffuse large B-cell lymphoma (DLBCL) and were heavily pre-treated with 57% having received three or more prior lines of therapy. Previously, results from the six patients treated in Cohort 1 (25M ACTR707+ T cells) and the three patients treated in Cohort 2 (40M ACTR707+ T cells) were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018. As presented at ASH (Free ASH Whitepaper), complete responses were achieved in three of six patients (50%) from Cohort 1 and a complete response was achieved in one of three (33%) patients from Cohort 2. The overall response rate, including complete and partial responses, was 50% in Cohort 1 and 67% in Cohort 2.

As a preliminary update provided today, for the five patients treated in Cohort 3 (55M ACTR707+ T cells), a complete response was achieved in one of five patients (20%) with overall responses in four of five patients (80%). The overall responses achieved in this cohort included evidence of deepening responses in two patients whose stable disease improved after the initial response assessment at day 42 to a partial and a complete response, respectively, as of the data cutoff in May 2019 (Table 1).
Table 1: ACTR707 Preliminary Phase 1 trial efficacy results in r/r NHL (Cohorts 1-3)
Clinical Response (1) Cohort 1
(n=6) Cohort 2
(n=3) Cohort 3
(n=5) Cohorts 1-3
(n=14)

Complete Response 3 1 1 36% (5/14)
Partial Response 0 1 3 29% (4/14)
Indeterminate Response 1 0 0 7% (1/14)
Progressive Disease 2 1 1 29% (4/14)
Overall Response Rate 50% (3/6) 67% (2/3) 80% (4/5) 64% (9/14)
ACTR707 + T cells administered per patient (range) 25M (23-38M) 40M (30-50M) 55M (45-55M)
(1) Data cutoff as of May 2019

Durable responses were observed in patients achieving a complete response with the durability of response ranging from 85-387+ days. In the first three cohorts, ACTR707 was well-tolerated in combination with rituximab. No dose-limiting toxicities (DLTs), no adverse events of cytokine release syndrome (CRS), and no severe neurological adverse events including neurotoxicity have been reported in Cohorts 1, 2 and 3 as of the May 2019 cutoff. Serious adverse events that were assessed by the investigator as possibly related to ACTR707 include two cases of febrile neutropenia and one case of cytopenia in Cohorts 1 and 2 (Table 2).

Table 2: ACTR707 Preliminary Phase 1 trial safety results in r/r NHL (Cohorts 1-3)

Safety Event (1) Cohort 1
(n=6) Cohort 2
(n=3) Cohort 3
(n=5)
Dose-limiting toxicities 0 0 0
Severe neurologic events (> Grade 3) 0 0 0
CRS (any grade) 0 0 0
ACTR707-related SAEs 1 2 0
febrile neutropenia 1 1 0
cytopenia 0 1 0
(1) Data cutoff as of May 2019

Cohort 4 (80M ACTR707+ T cells) enrollment proceeding in ATTCK-20-03: Enrollment in Cohort 4 of ATTCK-20-03 is complete and Unum plans to report updated results from ATTCK-20-03, including data from patients in Cohort 4, in late 2019.
ACTR707 Solid Tumor Program Highlights:

Phase 1 trial (ATTCK-34-01) with ACTR707 in HER2+ advanced solid tumor cancers ongoing: Clinical trial site activation, patient identification, screening and enrollment continues in the first dose cohort of ATTCK-34-01, a Phase 1, multicenter, open-label, single-arm, dose-escalation trial evaluating ACTR T cells (ACTR707) in combination with trastuzumab for the treatment of patients with HER2+ advanced cancers. Unum plans to report updates from the ATTCK-34-01 trial including patient enrollment status and preliminary safety data at the end of 2019.

Preclinical data demonstrate that, unlike traditional trastuzumab-based CAR-T cells that target HER2, ACTR707+ T cells administered with trastuzumab are highly selective for HER2-overexpressing tumor cells and discriminate against cells from normal tissues that express low levels of HER2. The preclinical activity of ACTR707+ T cell has been shown to be dose-dependent demonstrating control of ACTR707 activity by modulation of trastuzumab concentration. Together, the preclinical data suggest that ACTR cells in combination with trastuzumab may exhibit an improved clinical therapeutic index.

BOXR Solid Tumor Program Highlights:

Preclinical development ongoing for BOXR1030 targeting GPC3+ advanced cancers: Unum’s Bolt-On Chimeric Receptor (BOXR) platform is designed to improve engineered T cell functionality by identifying and incorporating a "bolt-on" transgene to overcome resistance of the solid tumor microenvironment to T cell attack. BOXR bolt-on transgenes identified in this platform are designed to address a variety of immunosuppressive mechanisms of solid tumors including metabolic competition, immune suppressor cells, and exhaustion due to chronic stimulation. These transgenes could offer the potential to add new functionality to T cells not achievable by traditional small molecule or antibody-based approaches. In addition, the BOXR bolt-on transgenes may be incorporated into several different types of therapeutic T cells, including ACTR T cells and CAR-T cells. Using a variety of BOXR bolt-on transgenes and tumor targeting technologies, Unum is building a pipeline of preclinical candidates to address a diverse range of solid tumor indications.

In early 2019, Unum nominated BOXR1030 as the first product candidate from the BOXR platform. In addition to research to further characterize its mechanism of action, preclinical studies of BOXR1030 are underway to support the filing of an investigational new drug (IND) application for BOXR1030. Unum plans to present preclinical data regarding BOXR1030 in the second half of 2019.
ACTR087 Hematologic Program Highlights:

Dose escalation continuing in Phase 1 (ATTCK-17-01) trial in multiple myeloma: Dose escalation continued during the second quarter in the ATTCK-17-01 trial combining ACTR087 with low doses of SEA-BCMA antibody. Enrollment and dosing of patients is complete in Cohort 4 (30M ACTR087+ T cells and 2.0 mg/kg SEA-BCMA) and Cohort 5 (50M ACTR087+ T cells and 2.0 mg/kg SEA-BCMA). Unum expects to report data from multiple dose cohorts in the second half of 2019.

Treatment continuing for responding patients in Phase 1 (ATTCK-20-2) trial in non-Hodgkin lymphoma: In July 2019, Unum announced that the U.S. Food and Drug Administration (FDA) placed a clinical hold (since communicated by the FDA as a partial clinical hold) on the Phase 1 trial (ATTCK-20-2) evaluating Unum’s ACTR087 in combination with rituximab in patients with CD20+ r/r NHL. The clinical hold was initiated following the submission of a safety report by Unum to the FDA regarding one patient in the safety expansion cohort of the trial who experienced serious adverse events including neurotoxicity, cytomegalovirus infection, and respiratory distress. As an update to this case, this patient subsequently experienced septic shock that was fatal and reported by the investigator as related to ACTR087. Patients who previously received ACTR087 and have ongoing clinical responses continue to receive rituximab infusions, with continued monitoring for adverse events. Unum continues to work closely with the FDA to further review these events and plans to report data from the ATTCK-20-2 trial at the end of 2019.
Corporate Highlights:

Announced new additions to its leadership team including Matthew Osborne as Chief Financial Officer, Mert Aktar as of Head of Business and Corporate Development and Jessica Sachs, M.D., as Chief Medical Officer replacing Michael Vasconcelles, M.D., who transitioned to a clinical advisory role. Each new executive has a proven track record of excellence and adds decades of experience to the Unum leadership team.

Announced the appointments of Arlene Morris and Matthew Ros to its Board of Directors. Ms. Morris and Mr. Ros replaced Robert Perez and Liam Ratcliffe, who transitioned from Unum’s Board of Directors in conjunction with their new positions within the biotechnology industry. Ms. Morris and Mr. Ross bring significant commercial, clinical and operational experience within the oncology field. Ms. Morris brings extensive corporate and business development experience in the pharmaceutical and biotechnology industries from numerous management and board roles, while Mr. Ros adds specific commercial experience, particularly with oncology products.

Entered into an agreement with Harbour Antibodies BV, a wholly-owned subsidiary of Harbour BioMed, granting Unum rights to utilize Harbour Antibodies’ H2L2 Harbour Mice platform. The agreement enables Unum to discover and incorporate fully-human antibody sequences into its novel ACTR and BOXR platforms to further enable and accelerate Unum’s preclinical discovery and development efforts.
Second Quarter 2019 Financial Results

Collaboration Revenue: Collaboration revenue recognized during the second quarter ended June 30, 2019 was $3.1 million, compared to $1.7 million in the same period of 2018. The increase reflects the recognition of a portion of the upfront payment received from Seattle Genetics, Inc. under Unum’s collaboration agreement as well as reimbursements of research and development costs attributed to the collaboration agreement.

R&D Expenses: Research and development expenses were $10.6 million for the second quarter ended June 30, 2019, compared to $9.1 million for the same period of 2018. The increase primarily reflects higher clinical trial costs for the active Phase 1 trials, as well as increased personnel-related costs.

G&A Expenses: General and administrative expenses for the second quarter ended June 30, 2019, were $3.1 million, compared to $2.0 million for the same period of 2018. The increase is primarily related to higher personnel related costs due to increased headcount and increased expenses around operating as a public company.

Net Loss: Net loss attributable to common stockholders was $10.5 million, or $0.34 per share, for the second quarter ended June 30, 2019, and $9.0 million, or $0.31 per share, for the same period of 2018.

Cash and Cash Equivalents: As of June 30, 2019, Unum had cash and cash equivalents of $55.9 million. Unum believes that its existing cash and cash equivalents will fund operating expenses and capital expenditure requirements into early 2021.
Investor Call and Webcast Information

Unum will host a live conference call and webcast today, August 12, 2019, at 4:30 p.m. ET, to discuss these financial results and company updates. To access the call, please dial 866-300-3411 (domestic) or 636-812-6658 (international) and refer to conference ID number 5658375. A webcast will be available at unumrx.com at least 10 minutes before the event begins. The archived webcast will be available at the same location approximately two hours after the event and will be archived for 90 days.

On August 12, 2019 Propanc Biopharma, Inc. (OTC: PPCB) ("Propanc"), a biopharmaceutical company developing new cancer treatments for patients suffering from recurring and metastatic cancer, reported that the company’s scientific researchers, together with its joint research partners, Universities of Jaén and Granada, published key data in a peer reviewed journal, Scientific Reports, confirming the mechanism of proenzymes and its anti-cancer effects against cancer stem cells (CSCs) (Press release, Propanc, AUG 12, 2019, View Source [SID1234538605]). From the publishers of Nature, it is an online, open access journal, which publishes primary research from all areas of the natural and clinical sciences. The article is entitled "Pancreatic proenzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumor engrafting," and can be accessed via the company website under the link: View Source

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"We are excited to publish this paper on our work with PRP and CSCs, where these cells drive cancer," said Dr Julian Kenyon, Propanc’s Chief Scientific Officer. "We were able to destroy these cells in significant numbers. Remarkably, we observed at least 13 genes that induce cancer were downregulated by PRP. Also, genes implicated in metastasis were downregulated and 7 genes related to cell adhesion, which is the normal state of healthy tissue, were upregulated. In summary, PRP has multiple modes of action, quite unlike any other cancer drug and is clearly in a class of its own. This is likely to translate into PRP being effective in many different cancer types and reducing the recurrence rate after standard treatments."

"Importantly, we proved that PRP impaired engrafting of human derived pancreatic CSC tumors in nude (immune compromised) mice, whilst also displaying an antigrowth effect toward initiated xenografts (grafted, human derived tumors), showing a decreased amount of tumor surrounding fibrotic tissue of treated mice," said Dr. Perán, Acting Professor at the Department of Health Sciences, University of Jaén and Propanc’s Scientific Advisor. "As cancer treatment moves towards more personalized medicine, proven therapies that target and treat specifically CSCs may prove to be a useful method for reducing recurrence after drug treatment failures."

The data provides the strongest evidence that proenzymes could be an effective tool in the fight against metastatic cancer, the single biggest cause of patient death for sufferers. The company’s lead product candidate, PRP, is a formulation of two proenzymes, designed to act synergistically against solid tumors which are malignant. PRP is currently in preparation for a First-In-Human study in advanced cancer patients which the company plans to commence in 2020.

To explain the significance of the discovery, people often have the misconception that tumors are made up from the same type of malignant cell that grows uncontrollably and exponentially. Although that could be the first impression when a tumors progress rapidly, in fact, tumors are a very complicated kind of new organ that develops an intricate organization with its own blood supply and an intricate communication system with the rest of the organism that facilitates the cancer dispersion. In addition, there are different types of cells within a tumor mass, it is true that all of them have a common feature, they are undifferentiated cells, but some of them are more "ancestral" than others. These cells are named cancer stem cells, or CSCs, and are responsible for tumor metastasis and tumor relapse. The strength of these particular cells is that they do not replicate, so conventional therapies that only affect growing cells, do not harm CSCs.

Other important facts about tumors is their ability to change their surroundings, inducing neighboring cells to become malignant, and even more worrisome, its ability to corrupt distant tissue cells creating a future tumor microenvironment.

After more than 10 years collaboration with Propanc’s prestigious, joint scientific researchers with significant experience in cancer, the company now understands the mechanism of action of PRP, a formulation containing a synergistic combination of two pancreatic proenzymes. The "beauty" of this naturally derived formulation is that the body has designed enzymes to perform a specific role on the cells to orchestrate gradual changes. In the same pathways that active enzymes work on healthy cells, PRP, once converted to the activated enzyme form, changes the malignant nature of cancer cells toward a differentiated state in which cells return to be what they were. Some of the company’s scientific studies have already been published in high impact journals, demonstrating that PRP decreases cell proliferation and migration, induces cell differentiation and impairs angiogenesis. In short, tumors cannot grow after PRP treatment, as demonstrated by in vivo studies with mice models.

This latest achievement has demonstrated that PRP also has a significant effect on that population of cells within the tumor that keep a dormant state and a stemness nature. As stated above, those cells, called CSCs, are not eradicated by conventional therapies and are responsible for generating a new tumor in other organs, a process known as metastasis, which is the main cause of patient death for sufferers.

"In collaboration with the Universities of Jaén and Granada, we have performed a detailed study on the effects of PRP upon these tumor-initiating cells and we are excited to reveal that our results are very encouraging," said Mr. James Nathanielsz, Propanc’s Chief Executive Officer. "In addition, we have proven a beneficial impact of our novel treatment, PRP, on tumor initiation and progression as well as on the tumor microenvironment, which is of great scientific interest."

The company has also been working with its research partners with the aim of enhancing the effects of PRP, whilst also maximizing a better-quality and safer product. The project is progressing well and on track to produce an optimized version of PRP which could be effectively reproduced with enhanced effects, compared to the naturally derived proenzymes. Further work is currently being undertaken to ensure the product is comparable in structure to PRP.

About the University of Jaén:

The University of Jaén is among the Top 50 of the best young universities in the world according to THE (Times Higher Education). Likewise, the University of Jaén received the EFQM 500+ European Seal of Excellence, the highest level of recognition awarded by the Excellence in Management Club, as the official representative of the European Foundation for Quality Management (EFQM) in Spain. It also stands out in the field of computing, since the University of Jaén is among the 75 best universities in the world, according to Academic Ranking of World Universities (ARWU) 2017. The University of Jaén is repeatedly in the top 4% of universities worldwide, according to the Ranking Center for World University Rankings (CWUR), which annually collects the thousand best and most valued among the more than 25,000 existing universities. In addition, it is the fourth Spanish university that has obtained the highest score in the ranking of international student satisfaction, published by the STEXX International Studyportals Organization, in its 2016 version.

About the University of Granada:

The University of Granada is widely recognized internationally for its quality in higher education, teaching, research and outreach. National and international rankings reflect the University Granada’s position among the top universities in Spain and among the best in the world. In 2018, the University of Granada has further consolidated this dominant position – taking 278th place in the world and 3rd in Spain in the recently published Shanghai Academic Ranking of World Universities (ARWU 2018). Viewed from the perspective of its performance in specific academic subjects, the UGR has also set a new record, with a further 34 subjects taught at the University featuring in the 2018 ARWU — 12 more than in 2017. Furthermore, 5 of the University Granada’s subjects feature among the world top 100, marking another significant milestone.